ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5’s function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing...

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Autores principales: Chen, Chunting, Zhai, Ertao, Liu, Yinan, Qian, Yan, Zhao, Risheng, Ma, Yan, Liu, Jianqiu, Huang, Zhixin, Chen, Jianhui, Cai, Shirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676604/
https://www.ncbi.nlm.nih.gov/pubmed/38007439
http://dx.doi.org/10.1186/s12935-023-03129-9
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author Chen, Chunting
Zhai, Ertao
Liu, Yinan
Qian, Yan
Zhao, Risheng
Ma, Yan
Liu, Jianqiu
Huang, Zhixin
Chen, Jianhui
Cai, Shirong
author_facet Chen, Chunting
Zhai, Ertao
Liu, Yinan
Qian, Yan
Zhao, Risheng
Ma, Yan
Liu, Jianqiu
Huang, Zhixin
Chen, Jianhui
Cai, Shirong
author_sort Chen, Chunting
collection PubMed
description The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5’s function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5’s demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03129-9.
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spelling pubmed-106766042023-11-25 ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer Chen, Chunting Zhai, Ertao Liu, Yinan Qian, Yan Zhao, Risheng Ma, Yan Liu, Jianqiu Huang, Zhixin Chen, Jianhui Cai, Shirong Cancer Cell Int Research The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5’s function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5’s demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03129-9. BioMed Central 2023-11-25 /pmc/articles/PMC10676604/ /pubmed/38007439 http://dx.doi.org/10.1186/s12935-023-03129-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Chunting
Zhai, Ertao
Liu, Yinan
Qian, Yan
Zhao, Risheng
Ma, Yan
Liu, Jianqiu
Huang, Zhixin
Chen, Jianhui
Cai, Shirong
ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title_full ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title_fullStr ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title_full_unstemmed ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title_short ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
title_sort alkbh5-mediated chac1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676604/
https://www.ncbi.nlm.nih.gov/pubmed/38007439
http://dx.doi.org/10.1186/s12935-023-03129-9
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